DESCRIPTION: Acute ischemic stroke is a major cause of disability among the elderly and the third leading cause of death. Reactive nitrogen species (NO an ONOO') are being increasingly implicated in the pathophysiology of cerebral ischemic-reperfusion injury. Since inducible nitric oxide synthase (iNOS) is a high output enzyme and it is active for days when induced, we hypothesize that NO produced by iNOS is an important factor in the pathophysiology of cerebral ischemic-reperfusion injury. We have identified a number of compounds (N-acetylcysteine, lovastatin, mevastatin and sodium phenylactic acid) that will prevent the neuronal injury when given prior to the onset of ischemia. Specific aim 2 is designed to investigate whether N-acetylcysteine will preven the neuronal injury by altering the course of the disease when given after the ischemic insult. These are relatively nontoxic compounds and are presently being prescribed for human consumption in other diseases. Therefore, demonstration of beneficial effects of these drugs in an animal model of cerebral ischemia-reperfusion injury will serve to identify as ideal candidate for use in clinical trials against cerebral ischemia and stroke. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE